This proposal is a K01 Mentored Scientist Development Award Application. The candidate, Dr. Mark W. Nowak, is an Assistant Professor in the Center for Drug and Alcohol Programs (CDAP) at the Medical University of South Carolina. A K01 award would allow the candidate to integrate his existing research skills in the study of nicotinic acetylcholine receptors (nAChRs) with the field of alcohol research. While the candidate has research experience in the study of nAChRs, he has no prior research experience in the alcohol field. The proposed training plan is designed to provide the candidate with a broad knowledge of alcohol-related research through didactic work, training in electrophysiological and tissue culture techniques specific to ethanol research, and "hands-on" training in the use of animal models involving in vivo ethanol exposure. Within CDAP, there are established researchers in the alcohol field, thus ensuring the successful completion of the training objectives. Further, the proposed research project described below complements these training objectives and addresses the candidate's research interests in developing an independent research program focused on nicotine-ethanol interactions. Understanding ethanol-nicotine interactions is a relevant health issue given the well-documented comorbid use of alcohol and tobacco products. While the reasons for the combined use of these substances are not well-understood, there is a growing body of evidence suggesting involvement of ethanol-nicotine interactions in the CNS. Ethanol and nicotine have been shown to affect a wide variety of neurochemical systems in the brain. The main CNS target for nicotine are the neuronal nAChRs. It is reasonable to suggest that neuronal nAChRs may, in part, be involved in central ethanol/nicotine interactions. Nevertheless, while the effects of ethanol on other ligand-gated ion channels (NMDA, GABAA and 5-HT3 receptors) have received considerable attention, the effects of ethanol on neuronal nAChR function have not been extensively studied. To address this research question, the proposed research studies will examine the effects of acute and chronic ethanol exposure on neuronal nAChR function. Electrophysiological whole-cell patch clamp techniques will be utilized to assess neuronal nAChR function in primary rat hippocampal neuronal cultures. The findings from the proposed studies will contribute to the long-term goal of understanding the effects of ethanol and nicotine on brain function. Overall, this K01 award would allow Dr. Nowak to expand his experimental skills into the field of alcohol research as well as achieve his goal of developing an independent research program studying alcohol-nicotine interactions.